Children's Hospital of Orange County (CHOC) was only recently approved as a full member institution (April 1993) in Childrens Cancer Group (CCG). Despite being a full member for only eighteen months, CHOC investigators have contributed significantly to the development of new therapeutic protocols, the establishment of two reference laboratories, and have provided significant scientific and administrative leadership within CCG. CHOC currently registers all eligible patients on to CCG protocols and is an approved CCG phase I and Bone Marrow Transplant institution. The long- term objective of this proposal is to further the improvement in the prevention, diagnosis, and treatment of childhood cancer through participation in CCG. The specific aims of this proposal include: l) providing leadership in several strategy groups, discipline committees, and study committees; 2) expanding the reference laboratories for lymphoma studies and hematopoiesis/cytokine translational research; 3) providing leadership and implementation of group phase I trials; and 4) developing pilot studies that can be translated and implemented into groupwide studies. There are presently 7 investigators at CHOC participating in 32 committee appointments. The recruitment of additional CHOC investigators will provide additional scientific and administrative CCG leadership at the level of the strategy group, study chair, study vice chair, and within scientific and discipline committees. The CHOC Hematopoisis/Cytokine Laboratory will continue to investigate stem cell regulation and cytokine receptor modulation, develop methods for ex vivo isolation and expansion of stem cells (CD34), and optimize the mobilization of peripheral stem cells for repetitive submyeloablative therapy. The Lymphoma Reference Laboratory will continue to investigate the oncogenesis of childhood lymphomas and develop alternative treatment strategies, including antisense gene therapy for Burkitt's lymphoma. Pilot phase I trials in biotherapy, immunotherapy, and hematopoiesis, including lL-2 and activated leukocytes, IL-12 + IL-15 immunotherapy, auto-graft-vs-host tumor induction, and the use of new cytokines, including thrombopoietin, will be explored at CHOC and will potentially lead to groupwide studies. In summary, CHOC will continue to provide leadership for pilot studies through CCG, participate in all open CCG phase I, II, III, and bone marrow transplant studies, develop protocols for determining the long-term effects of chemo-radiotherapy and immunotherapy, and conduct specific biological investigations in the areas of experimental hematopoiesis and childhood lymphoma.